Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.
Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.
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DOI：
10.1038/srep32972
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发表时间：
2016-09-06
影响因子：
4.6
通讯作者：
Liu HL
中科院分区：
文献类型：
--
作者：
Gao YT;Chen XB;Liu HL
MicroRNAs(MiRNA)被认为在多形性胶质母细胞瘤(GBM)化疗中起着重要作用。我们的研究旨在探讨GBM中潜在的miRNA生物标志物。60例GBM患者接受替莫唑胺(TMZ)化疗和复发放疗。在癌组织和配对的正常组织中进行miRNA阵列。微阵列结果通过在选定的组织和GBM细胞系中的实时定量聚合酶链式反应进一步验证。建立TMZ耐药细胞，并进行细胞增殖和集落形成实验。本研究采用H_2AX形成和流式细胞术分析miRNA在DNA损伤和细胞凋亡中的作用。我们的研究显示了16个miRNA，其中9个上调，7个下调。在复发的肾小球基底膜组织中发现了它们的差异表达。其中，miRNA-370-3p在组织和TMZ耐药细胞中下调水平最高。MiRNA-370-3p模拟物通过抑制肿瘤细胞DNA的自我修复能力，增加其表达，增强GBM细胞对TMZ的敏感性。O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)被确定为miR-370-3p的直接靶基因，并发现它与miR-370-3p在组织样本中的表达呈负相关。因此，我们的研究证实了miR-370-3p表达上调在多形性胶质母细胞瘤化疗敏感性中的关键临床作用。
MicroRNAs (miRNA) are believed to play an important role in glioblastoma multiforme (GBM)chemotherapy. Our study aims to investigate potential miRNA biomarkers in GBM. Sixty GBM patients, which were given temozolomide (TMZ) chemotherapy and recurrent radiotherapy, were recruited. miRNA array was performed in cancerous and in paired normal tissues. Microarray results were further validated by a quantitative real-time PCR in selected tissues and GBM cell lines. TMZ resistance cells were developed and cell proliferation along with colony formation assays was determined. Our study employed H2AX formation and flow cytometry to analyse the role of miRNA in DNA damage and apoptosis. Our study illustrated 16 miRNA in which 9 were up-regulated and 7 down-regulated. and their differential expression were demonstrated in a recurrent GBM tissue. Among them, miRNA-370-3p demonstrated the highest level of down- regulation in tissues and in TMZ resistance cells. miRNA-370-3p mimic increased its expression and sensitivity of GBM cells to TMZ by suppressing the self-reparative ability of tumour cell DNA. O6-methylguanine-DNA methyltransferase (MGMT) was identified as the direct target gene of miR-370-3p, and it was found to be inversely correlated with miR-370-3p expression in tissue samples obtained. Thus, our study demonstrated a critical clinical role of an up-regulated miR-370-3p expression in glioblastoma multiforme chemotherapy sensitivity.
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DOI：
10.3322/caac.20069
发表时间：
2010-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Van Meir EG;Hadjipanayis CG;Norden AD;Shu HK;Wen PY;Olson JJ
通讯作者：
Olson JJ
影响因子：
5.1
作者：
Gonzalez-Gomez, Pilar;Sanchez, Pilar;Mira, Helena
通讯作者：
Mira, Helena
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
168.9
作者：
Ricard, Damien;Idbaih, Ahmed;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves
影响因子：
3.7
作者：
Wu Z;Sun H;Zeng W;He J;Mao X
通讯作者：
Mao X